Table 1.

Involvement of Hsp65 in the pathogenesis of autoimmune and other immune-mediated disorders

Disease	Host	Origin of Hsp	Effector mechanism	Reference
Autoimmune arthritis (e.g., A A )	Rat	Mtba	Mtb immunization leads to activation of Bhsp65- reactive T cells, which are then restimulated in the joint by a cartilage protein (molecular mimicry)	[7,9, 10, 13, 15]
Atherosclerosis	Human Rabbit Mouse	C. pneumoniae, Human, Mtb	Microbial Hsp65 triggers antibody and T cell responses that are crossreactive (molecular mimicry) with self Hsp65 over-expressed in vascular endothelial cells in atherosclerotic lesions	[4, 5, 20-23]
Autoimmune diabetes	Mouse, Human	Human, Mouse, Mtb	T cell response against self Hsp65/Bhsp65 is induced spontaneously in NOD mice and in T1D patients. These T cells home to the pancreatic beta islets, where self Hsp65 serves as the target antigen (along with GAD65 and insulin).	[25-27]
Autoimmune intestinal inflammation	Mouse	Mtb, Mouse	CD8+ T cells specific for Hsp65, upon adoptive transfer, migrate to the intestinal mucosa where recognition of self Hsp65 triggers autoimmune inflammation	[30]
Autoimmune demyelination (e.g., EAE)	Rat	Mtb	T cells reactive against myelin-basic protein and its epitope 71-90 as well as Bhsp65 are enriched in the spinal cord of the diseased rats	[31]
Juvenile dermatomyositis	Human	Human, Mtb	The production of TNF-α, IL-1β and IL-10 in response to Hsp65 is significantly increased in active disease compared to inactive disease; both effector and regulatory T cells are present at the inflammatory site	[34]
Renal transplant: graft rejection	Human	Human	A change in the cytokine response to Hsp65 in favor of anti-inflammatory IL-4 with time post-transplant; IL-4 is associated with absence of graft rejection.	[36]

^aAbbreviations: AA: Adjuvant arthritis; C. pneumoniae: Chlamydia pneumoniae; EAE: experimental autoimmune encephalomyelitis; GAD 65: glutamic acid decarboxylase 65; Hsp: heat shock protein; IL : interleukin; Mtb: Mycobacterium tuberculosis; NOD: non obese diabetic; TNF-α tumor necrosis factor-alpha; T1D : type 1 diabetes.